Evidence map›Paper›PMID 40770890›Full record

ArticleClinical and experimental reproductive medicine2026

The role of nGPx4 in resisting DEHP-induced DNA damage and reducing caspase-independent cell death in male germ cells.

Wei Gu, Jiaxin Wang, Xinqi Liu, Huizhe Tan, Hongming Yang, Zeshan Zhu, Peng Ran, Qing Ling, Weilin Mao

Abstract read
In one paragraph

Article in Clinical and experimental reproductive medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Wei GuDepartment of Urology, Minda Hospital of Hubei Minzu University, Enshi, China.
Jiaxin WangDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Xinqi LiuDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Huizhe TanDepartment of Urology, Minda Hospital of Hubei Minzu University, Enshi, China.
Hongming YangDepartment of Urology, Minda Hospital of Hubei Minzu University, Enshi, China.
Zeshan ZhuMedical School, Hubei Minzu University, Enshi, China.
Peng RanMedical School, Hubei Minzu University, Enshi, China.
Qing LingDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Weilin MaoDepartment of Urology, Minda Hospital of Hubei Minzu University, Enshi, China.

Funding

Enshi Tujia and Miao Autonomous Prefecture Bureau of Science and Technology XYJ2020000061Hubei Provincial Natural Science Foundation 2022CFB255
6 · The paper itself

Abstract

objectiveDi(2-ethyl-hexyl) phthalate (DEHP) is a widely used plasticizer that adversely affects sperm quality and function by inducing DNA damage and caspase-independent cell death (CICD). Nuclear glutathione peroxidase 4 (nGPx4) has been implicated in maintaining the structural integrity of sperm chromatin. However, it remains unclear whether nGPx4 can counteract the DNA damage caused by DEHP exposure.

methodsWe employed a germ cell line (GC-1) spg mouse cell model engineered to overexpress nGPx4 (OE-nGPx4). The cells were subsequently exposed to DEHP and its metabolite mono-2-ethylhexyl phthalate (MEHP) to simulate the DNA-damaging effects of environmental factors on reproductive cells. Following treatment, we assessed the proportion of apoptotic cells and the extent of DNA damage using molecular biological analyses, in addition to evaluating the expression of proteins associated with the apoptotic pathway in germ cells.

resultsnGPx4 overexpression protected against DEHP-induced DNA damage in germ cells, reducing the incidence of CICD and potentially preserving sperm quality. This protective effect was mediated by enhanced chromatin condensation in mouse sperm cells and downregulation of phosphorylated H2A histone variant (γ-H2A.X). The reduction in DNA degradation is attributed to a diminished formation of the complex between γ-H2A.X and apoptosis-inducing factor (AIF), resulting in decreased DNA fragmentation. Additionally, compared to MEHP-treated cells, OE-nGPx4 cells exhibited reduced expression of Bcl 2-associated X (Bax), thereby diminishing activation of the γ-H2A.X/AIF axis.

conclusionOur findings suggest that nGPx4 is involved in chromatin condensation and may contribute to downregulating the AIF/γ-H2A.X axis in male germ cells, ultimately reducing DNA damage-induced CICD.

Indexed as

Caspase-independent cell deathDNA condensationDNA damagenGPx4Sperm quality

Identifiers

PMID40770890
PMCPMC12954061

What Socratic holds

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